For every title, a question mark. The latest HIV science story providing fodder for excitable journalists is highlighted in today’s Kaiser Daily Update (see HIV Replicating at Slower Rate, Could Be Weakening, Study Says). The news stories relate to a study published in the October 14 issue of AIDS that attempts to compare the relative “fitness” of HIV sampled during the period 1986-1989 to viruses obtained more recently (2002-2003). The authors of the paper, comprising teams from Belgium and the US, conclude that there is evidence that HIV is weakening over time. One even went so far as to be quoted suggesting that HIV may no longer be a fatal infection in 60 years time. Predictably, these conclusions have been a magnet for publicity. But do they stand up to scrutiny?
The reported results are from test tube experiments that assess the relative fitness of HIV viruses using a “growth competition assay.” Two viruses are placed in a lab dish that can support replication and after 10 days the total amount of each virus is measured as well as the ratio between the two viruses (e.g. if one HIV isolate produces twice as much virus as the other the test would say that virus is about twice as fit) . A total of 24 viruses were studied, 12 from 1986-1989 and 12 from 2002-2003. In most of the experiments (176 out of 238 that were conducted), the older viruses outcompeted the recent viruses. The researchers also calculate a “mean relative replicative fitness” score for the older and newer HIVs; for the older samples the score was 1.395 while for the recent samples it was 0.545. In other words, the researchers estimate that HIV used to be more than twice as “fit” than it is today.
This is undoubtedly a great-sounding story, and one that fits with models that suggest that new infectious agents like HIV are likely to become less harmful to their human hosts over time. However – and it is a big however - the link between test tube measurements of viral fitness and HIV’s ability to cause disease is far from clear. Exactly the same type of test tube experiment has shown that HIV from subtype C (prevalent in Africa and India) is less fit than HIV from subtype B (prevalent in North America and Europe). The difference in the relative replicative fitness scores was very similar to those described above for the older and newer HIVs. Yet there is no evidence that individuals infected with subtype C experience slower disease progression. In fact, one study reported that individuals infected with subtype C HIV may have higher viral loads on average than those infected with other subtypes.
So, to return to the question, is HIV weakening over time? Maybe, but this study cannot provide a clear answer one way or the other.
Replicative fitness of historical and recent HIV-1 isolates suggests HIV-1 attenuation over time. AIDS. 19(15):1555-1564, October 14, 2005. Arien, Kevin K; Troyer, Ryan M; Gali, Youssef; Colebunders, Robert L; Arts, Eric J; Vanham, Guido
Background: Changes in virulence during an epidemic are common among pathogens, but still unexplored in the case of HIV-1. Here we used primary human cells to study the replicative fitness of primary HIV-1 isolates from untreated patients, comparing historical (1986-1989) and recent samples (2002-2003).
Methods: Head-to-head dual virus infection/competition assays were performed in both peripheral blood mononuclear cells and human dendritic cell/T-cell co-cultures with pairs of 12 carefully matched historical and recent HIV-1 isolates from untreated patients. Sensitivity to inhibition by lamivudine (3TC) and TAK-779 of historical and recent R5 HIV-1 isolates was measured in a subset of samples.
Results: Overall, the historical HIV-1 out-competed the recent HIV-1 isolates in 176 of 238 competitions and in 9 of 12 competitions carefully matched for CD4 cell count. The mean relative replicative fitness (W) of all historical HIV-1 strains was significantly greater than that of recent HIV-1 isolates (W1986-1989 = 1.395 and W2002-2003 = 0.545, P < 0.001 (t test)). The more fit viruses (mean W > 1) from 1986-1989 appeared less sensitive to TAK-779 and 3TC than did the less fit (mean W < 1) 2002-2003 viruses.
Conclusions: These findings suggest that HIV-1 replicative fitness may have decreased in the human population since the start of the pandemic. This 'attenuation' could be the consequence of serial bottlenecks during transmission and result in adaptation of HIV-1 to the human host.